Genome wide binding sites of Smad3 and JMJD3 in neural stem cells

Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFß pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFß-responsive genes. In vivo experiments in chick spinal cord revealed that the generation of neurons promoted by Smad3 is dependent on JMJD3 HDM activity. Overall, these findings indicate that JMJD3 function is required for the TGFß developmental program to proceed. Overall design: We immunoprecipitate endogenous Smad3 or JMJD3 proteins from neural stem cells treated with TGFb for 30 minutes.